Volume 17, Issue 2: Spring 2021 by Columbia Science Review

COLUMBIA SCIENCE REVIEW SPRING 2021 Volume 17 Issue II

Cover illustrated by Vanshika Sriram Layout Editor (Articles): Alejandra Nunez (Episodic Memory), Amanda Klestzick (DeepMind and Protein Folding), Christine Shao (Letters + Table of Contents), James Yin (Colloidal Nanoparticles), Kevin Li (Chemistry of Baking), Lia Chen (Believe Me), Maria Nunez (Allergic Reactions)

Fair Use Notice Columbia Science Review is a student publication. The opinions represented are those of the writers. Columbia University is not responsible for the accuracy and contents of Columbia Science Review and is not liable for any claims based on the contents or views expressed herein. All editorial decisions regarding grammar, content, and layout are made by the Editorial Board. All queries and complaints should be directed to the Editor-In-Chief. This publication contains or may contain copyrighted material, the use of which has not always been specifically authorized by the copyright owner. We are making such material available in our efforts to advance understanding of issues of scientific significance. We believe this constitutes a “fair use” of any such copyrighted material, as provided for in section 107 of the US Copyright Law. In accordance with Title 17 U.S.C. Section 107, this publication is distributed without profit for research and educational purposes. If you wish to use copyrighted material from this publication for purposes of your own that go beyond “fair use,” you must obtain permission from the copyright owner.

EDITORIAL BOARD EDITOR-IN-CHIEF SARAH HO CHIEF DESIGN OFFICER AIDA RAZAVILAR CHIEF ILLUSTRATOR LIZKA VAINTROB EDITORS AIDA RAZAVILAR, ANNA CHRISTOU, CHERYL PAN, EDWARD KIM, EMILY SUN, ENOCH JIANG, ETHAN WU, KIMIA HEYDARI, LUCAS MELO, PATRICK TONG, NINA LILOIA, RACHEL POWELL, SARAH BOYD, SASHA HE, SERENA CHENG ILLUSTRATORS AEJA ROSETTE, CHERIE LIU, KARENNA CHOI, KATE STEINER, MEGAN ZOU, NICOLE LIN, REBECCA SIEGEL, SABRINA RUSTGI, TIFFANY QIAN, VANSHIKA SRIRAM, YI QU, ZOE HEIDENRY

MANAGING EDITOR LINGHAO KONG WRITERS ALAN ZHAO, ALLISON LIN, ANGEL LATT, ANGELA MU, ANUVA BANWASI, APARNA KRISHNAN, CHARLES BONKOWSKY, CLARE NIMURA, ELAINE ZHU, ELEANOR LIN, ELLEN ALT, ETHAN FENG, HANNAH PRENSKY, JEFFREY XIONG, JENNA EVERARD, JIMMY LIU, JOSHUA YU, KEVIN WANG, MICHELLE LU, SHIVANI TRIPATHI, TANISHA JHAVERI, TAYLOR BRIGGS, VICTORIA COMUNALE, YILYN CHEN LAYOUT EDITORS ALEJANDRA NUNEZ, AMANDA KLESTZICK, CHRISTINE SHAO, JAMES YIN, KEVIN LI, LIA CHEN, MARIA NUNEZ

EXECUTIVE BOARD PRESIDENT JASON WANG PUBLIC RELATIONS JOHN NGUYEN SECRETARY AROOBA AHMED TREASURER KAT WU SENIOR OCM ABHISHEK SHAH, ALLI GREENBERG, HANNAH LIN MEDIA TEAM BRENDON CHOY, CHENOA GALE BUNTS-ANDERSON, MAGGIE ZHONG, NICK ZUMBA

VICE PRESIDENT ADRIANA KULUSIC-HO OCMs AIDA RAZAVILAR, ALANA PALOMINO, BOYUAN CHEN, CHINMAYI BALUSU, CHRISHON CAMPBELL, EMILY KHINE, ESME LI, EVERETT MCARTHUR, JOJO WU, JOSHUA YU, PRANAY TALLA, SAVVY VAUGHAN-WASSER, SONALI DASARI

The Executive Board represents the Columbia Science Review as an ABC-recognized Category B student organization at Columbia University.

TABLE TABLE OF OF CONTENTS CONTENTS Spring 2021

Letters from the Editors

Cocktail Articles

SARAH HO & LINGHAO KONG

JEFFREY XIONG, RACHEL POWELL, ANGEL LATT, NINA LILOIA

How Tiny Nanoparticles Help Us Fight Big Problems ETHAN FENG

Allergies

Believe Me

Memory and Its Nuances

The Chemistry of a Chocolate Chip Cookie

VICTORIA COMUNALE

SHIVANI TRIPATHI

ALLY LIN

CLARE NIMURA

The Protein Folding Question ANUVA BANWASI

FROM THE FROM THE Dear Reader, Hello and welcome to the Columbia Science Review’s Spring 2021 print issue! This semester, our writers, editors, illustrators, and layout editors have highlighted a number of fascinating topics in science. As you flip through the pages of our issue, you will see articles that break down the chemistry of baking, explain how artificial intelligence is solving the protein-folding problem, and showcase the many applications of nanoparticles to our everyday lives. These topics—as well as those covered by the many other articles in this issue—are by no means simple to explain or understand, but the Editorial Board staff has done an incredible job in presenting them in a clear and exciting way. This is the fourth issue that the Columbia Science Review has published during the pandemic and I am extremely impressed by the effort and hard work that everyone on the Editorial Board has invested into this issue. All of us have felt the fatigue and exhaustion of over a year of isolating, quarantining, and mask-wearing, not to mention the demands of a difficult academic semester, so I remain grateful to every member of the Editorial Board who continued to make time for the Columbia Science Review. This marks my fourth and final year with the Columbia Science Review Editorial Board, and I’d like to thank everyone who helped make this organization such a vital and exciting part of my time at Columbia. In particular, I would like to extend a hearty congratulations to my fellow graduates, some of whom I’ve known ever since my freshman fall: Ellen Alt, Serena Cheng, Anna Christou, Enoch Jiang, Amanda Klestzick, Cheryl Pan, and Lizka Vaintrob. Thank you for all of your support and friendship, both within and outside of the Columbia Science Review. While I’m sad to be leaving, I’m also very excited to pass the baton onto Linghao Kong as the next Editor-in-Chief, who I’m confident will do an excellent job. I can’t wait to see what the Columbia Science Review does next! Love,

Sarah Ho Editor-in-Chief 6

EDITORS EDITORS Dear Reader, Welcome to the Spring 2021 print issue of the Columbia Science Review! I hope you enjoy reading it just as much as we did creating it and that your interest and imagination are captured by articles ranging from nanoparticles to baking. The importance of scientific literacy in the face of fear and uncertainty has been greatly highlighted this past year, and we hope that, even as such fear and uncertainty subsides, the increased scientific literacy will persist. As hope for the end of the pandemic grows, we have decided to focus on topics not related to COVID-19 itself. However, you can still find much information about the novel coronavirus and its impacts in our Fall 2020 and special COVID-19 edition publications. Despite remaining challenges, I am incredibly thankful for our writers, editors, illustrators, and layout designers who have come together to make something far greater than the sum of its parts. Without the dedication and hard work of our team, we would not be able to create these publications with such consistency. Thank you so much for reading our work, and I hope you stay safe! Sincerely,

Linghao Kong Managing Editor

Green Science, Gray Cities Written by Jeffrey Xiong Illustrated by Yi Qu

The fabric that holds cities together is concrete. By some estimates, the total mass of concrete in the world has exceeded the mass of all the trees and shrubs in the world combined [1]. It is the second most used singular resource in the world (just behind water), and 70 percent of the global population lives in a concrete building [2]. All around the world, the vast majority of greenery is replaced with the painted-over-gray of concrete. But the green cost of this gray is great. Concrete, being as prevalent as it is, is one of the largest contributors to global warming in the world today— between 8 to 10 percent of all the world’s carbon dioxide production stems from concrete alone [3]. To produce concrete, it is necessary to heat materials to thousands of degrees Fahrenheit constantly, a process which consumes a great deal of energy. This energy is largely fueled by the burning of fossil fuels. Furthermore, the chemistry of cement necessarily produces a tremendous amount of carbon dioxide. One of the key ingredients of cement is lime (calcium oxide or CaO), which can only be produced on a large scale by heating limestone (calcium carboxide or CaCO3), which makes carbon dioxide (CO2) as a byproduct [4]. The result is devastating: in just two years, the carbon footprint of concrete production matches the carbon footprint of all of the plastic that has been produced since the end of World War 2 [1]. Furthermore, concrete also consumes almost 10 percent of all the world’s water [1]—water that disproportionately comes from areas already prone to drought [5]. Unfortunately, there isn’t really a way around this—water is required in every facet of concrete, from making it to transporting it to smoothing out its settling. Combined, these inherent factors of concrete production and its present necessity pose a major roadblock in the fight against climate change. There are some modern proposals to reduce the environmental impact of concrete: certain new types of concrete, albeit less

sturdy, decrease the need for water or heat by recycling old materials or by utilizing a different composition of materials[3]. Furthermore, green urbanism, the integration of environmental structures into the fabric of cities, can de-emphasize the need to even use concrete by rethinking urban planning and construction in radical ways[6]. Although these steps towards greener building materials are currently limited in scope, it is important to recognize that concrete is an enormous source of carbon dioxide production, both locally and globally, and even more so as climate change intensifies. These are questions that are of vital importance whenever new infrastructure policies get passed or expanded. For a greener Earth, the gray may need to go.

When Social Beings Boredom and Quarantine: How Loneliness Affect the Brain

Written by Rachel Powell

Illustrated by Tiffany Qian

After more than a year since the start of the COVID-19 pandemic, it’s safe to assume that, by now, most people have become very familiar with feelings of boredom and loneliness. Adhering to social distancing guidelines means working or learning from home, primarily seeing friends through a screen, and spending more time indoors. Boredom and loneliness are typically temporary and harmless, but they can be detrimental to mental and physical health when they persist over long periods of time. Loneliness affects the brain in several important ways, contributing to a higher risk of depression, high blood pressure, low quality of sleep, and stress [1]. The impacts of loneliness can be seen in the midbrain, the part of the brainstem associated with functions such as sleep and alertness [2]. When a person is feeling isolated, dopamine-producing neurons in the midbrain are more active when responding to images of people socializing [2]. Loneliness also triggers a “self-preservation mode” in the brain, making people more likely to feel sensitive, vulnerable, and threatened when facing everyday social situations [1].

New and existing technologies and platforms have been utilized over the last year to foster more human connection and alleviate boredom, decreasing feelings of isolation and increasing productivity. More groups of friends are currently using apps like Google Duo and Houseparty than before the pandemic, and Twitch, a live streaming platform for gamers, has seen a significant increase in traffic [5]. From Zoom study rooms to virtual museum tours, more people are using their smartphones and computers to meet new people and have new experiences. While isolation and lack of stimulation can be harmful for mental and physical health, they can also motivate people to seek out opportunities to socialize and add excitement to their daily lives [4]. When people can achieve this virtually, they can reduce or avoid some of the negative effects of loneliness and boredom while also adhering to public health guidelines.

While researchers have yet to come to a clear consensus on how to define boredom, a 2012 study in the Educational Psychology Review proposes a twodimensional definition: “Sub-optimal arousal coupled with unpleasant emotions” [3]. Feeling bored, according to psychologist John Eastwood, can also be described as having an “unengaged mind” [4]. Depending on a person’s situation, boredom can manifest as drowsiness, restlessness, negative thinking, anxiety, or a lack of productivity [4]. This is why boredom over a long period of time can look—and feel—much like depression. While boredom and depression are distinct states of low arousal, they are highly correlated [4]. Boredom can also negatively affect an individual’s performance in professional and academic settings [4].

Psychological Pills Written by Angel Latt Illustrated by Lizka Vaintrob

Your head is pounding. You can’t focus on the task in front of you. Your hand stretches in agony toward the bottle of Tylenol that is calling your name. The pills roll softly on your tongue and down your throat with a gulp of water, and somehow you instantly feel a sense of relief. A surge of determination propels you to keep working, the pain diminished and left in the past. Psychologists and scientists alike call this phenomenon “the placebo effect.” Along with the pharmaceutical effects of treatments and drugs, the act of taking a substance alone can unintentionally convince your mind that you have been cured. However, placebos alone don’t shrink tumors or alleviate migraines. They can only go so far in making someone

feel better. The power of the placebo comes from playing with symptoms regulated by the brain, such as the perception of pain [1]. The term placebo often conjures images of white pills or sugar tablets, but placebos are not limited to physical medications. Placebos include words, social and physical cues, internal expectations, memories, and emotions. The clinical setting of placebo administration is pivotal to the effect [2]. For example, the visual and auditory cues in a doctor’s office of a physician administering a drug will elicit positive expectations about your treatment. The placebo effect is also analyzed through a Pavlovian lens of conditioning and reinforcement systems —“after going to the doctor previously, I’ve felt better, so I must this time as well” [3]. The placebo effect has many neurobiological implications. This phenomenon involves many neurotransmitter systems like opiate and dopamine and activates specific brain regions designated for pain sensation and perception. In a study of patients with Parkinson’s, dopamine release was amplified with a placebo acting as a dopaminergic agent [4]. Further neuroimaging data has shown activation in cortical regions of the brain after placebo administration [3]. The placebo effect uses an extensive neural network known as the descending pain modulatory system, which consists of various brain regions that regulate sensation to the central nervous system as well as pain response [5]. Additional research also points toward effects on the amygdala, a key player in fight-or-flight, where placebo treatments increase endogenous opioid responses [2]. The placebo effect goes a long way toward understanding healing and therapeutics. Placebos are simply another addendum to the ever-growing evidence of the healing power of the mind.

The Agtech Buzz: Written by Nina Liloia Illustrated by Sabrina Rustgi

How Tech Companies Are Modernizing Honeybee Usage

Honeybees are incredible contributors to our diets and our economy. They pollinate approximately 90 different crops in North America, allowing us to mass-produce our favorite foods — coffee, apples, almonds, and oranges are just a few examples [1, 2]. Additionally, through bees’ pollinating and their production of honey, beeswax, pollen, and propolis, Forbes estimates that honeybees contribute approximately 20 billion dollars to the global economy [3]. Despite their importance, honeybee populations are at risk. According to Sammy Ramsey, a honeybee researcher at the U.S. Department of Agriculture, bees are threatened by “a triangle of factors called the three Ps… parasites, pesticides and poor nutrition” [2]. A phenomenon called “colony collapse,” in which worker bees abandon their hives, is also decimating hives for unknown reasons [4]. Researchers think that the three Ps, as well as loss of habitat and lack of genetic diversity, could be driving colony collapse [4]. The “agtech’’ sector is composed of companies that create and utilize technology to make agriculture more efficient, sustainable, and profitable. Some agtech companies are attempting to both combat honeybee loss and make bees more efficient pollinators. To curb colony collapse, the Isreali startup BeeHero has created sensors that can monitor the condition, behavior, and efficiency of hives [5]. Information is accessible through an online dashboard, and monitored statistics include temperature, humidity, sound, the amount of pollen brought back to the colony, and the behaviors of bees in the hive [5]. This means that beekeepers do not have to manually check every hive, saving labor and time and allowing colony collapse to be detected early enough that rescuing the hive is possible [5].

Another new agtech development called “bee vectoring” involves using bees to distribute organic pesticides. The company Bee Vectoring Technologies International (BVT) uses bees to disperse Vectorite, an EPA-approved powder containing the spores of the fungus Clonostachys rosea (CR-7) that protects crops from other, harmful fungi [6]. The bees walk through a tray of Vectorite when they leave their hive and drop it on plants’ blooms as they pollinate them [7]. Unlike synthetic chemical pesticides, CR-7 is safe for bees and other pollinators, as well as for human consumption [6]. Agtech companies like BeeHero and BVT are creating new hope for the survival of honeybees. The effort to save pollinators is important in securing enough food for our growing world.

Green Science Gray Cities

Psychological Pills

[1]Watts, J. (2019, February 25). Concrete: The most destructive material on earth. Retrieved May 05, 2021, from https://www.theguardian.com/cities/2019/feb/25/concrete-the-most-destructive-material-on-earth [2] Concrete Facts. (2015). Concrete facts. Retrieved May 05, 2021, from http://concretehelper.com/concrete-facts/ [3] Suhendro, B. (2014). Toward green concrete for better sustainable environment. Procedia Engineering, 95, 305320. doi:10.1016/j.proeng.2014.12.190 [4] Timperley, J. (2018, September 14). Q&a: Why cement emissions matter for climate change. Retrieved May 05, 2021, from https://www.carbonbrief.org/qa-why-cementemissions-matter-for-climate-change [5] Timperley, J. (2018, September 14). Q&a: Why cement emissions matter for climate change. Retrieved May 05, 2021, from https://www.carbonbrief.org/qa-why-cementemissions-matter-for-climate-change [6] Steffen Lehmann (September 6th 2011). What is Green Urbanism? Holistic Principles to Transform Cities for Sustainability, Climate Change - Research and Technology for Adaptation and Mitigation, Juan Blanco and Houshang Kheradmand, IntechOpen, DOI: 10.5772/23957. Available from: https://www.intechopen.com/books/ climate-change-research-and-technology-for-adaptation-and-mitigation/what-is-green-urbanism-holistic-principles-to-transform-cities-for-sustainability

[1] The power of the placebo effect - Harvard Health. (2021). Retrieved from https://www.health.harvard.edu/ mental-health/the-power-of-the-placebo-effect [2] Wager, T. and Atlas, L., 2015. The neuroscience of placebo effects: connecting context, learning and health. Nature Reviews Neuroscience, 16(7), pp.403-418. [3] Benedetti, F., Carlino, E. and Pollo, A., 2010. How Placebos Change the Patient’s Brain. Neuropsychopharmacology, 36(1), pp.339-354. [4] Oken, B., 2008. Placebo effects: clinical aspects and neurobiology. Brain, 131(11), pp.2812-2823. [5] The influence of the descending pain modulatory system on infant pain-related brain activity. (2021). Retrieved from https://elifesciences.org/articles/37125#:~:text=The%20 descending%20pain%20modulatory%20system%20 (DPMS)%20constitutes%20a%20network%20of,and%20 behavioural%20responses%20to%20pain

When Social Beings Quarantine [1] Henig, R. M. (2014, August 11). The Science of Loneliness. Psychology Today. https://www.psychologytoday.com/us/ blog/cusp/201408/the-science-loneliness [2] Brookshire, B. (2020, November 23). Lonely brains crave people like hungry brains crave food. Science News. https:// www.sciencenews.org/article/lonely-brains-social-isolation-people-mental-health [3] Vogel-Walcutt, J. J., Fiorella, L., Carper, T., & Schatz, S. (2012). The Definition, Assessment, and Mitigation of State Boredom Within Educational Settings: A Comprehensive Review. Educational Psychology Review, 24, 89–111. https:// doi.org/10.1007/s10648-011-9182-7 [4] Weir, K. (2013, August). Never a dull moment: Things get interesting when psychologists take a closer look at boredom. Monitor on Psychology, 44(7), 54. [5] Koeze, E., & Popper, N. (2020, April 7). The Virus Changed the Way We Internet. The New York Times. https:// www.nytimes.com/interactive/2020/04/07/technology/ coronavirus-internet-use.html

The Agtech Buzz [1] The White House: Office of the Press Secretary. (2014, June 20). Fact sheet: The economic challenge posed by declining pollinator populations [Fact sheet]. The White House: President Barack Obama. Retrieved March 29, 2021, from https://obamawhitehouse.archives.gov/ the-press-office/2014/06/20/fact-sheet-economic-challenge-posed-declining-pollinator-populations [2] Sofia, M. (Host). (2020, April 2). Honeybees need your help, honey [Audio podcast transcript]. In Short wave. NPR. https://www.npr.org/transcripts/825305756 [3] The value of pollinators to the ecosystem and our economy. (2019, October 14). Forbes. Retrieved March 29, 2021,from https://www.forbes.com/sites/bayer/2019/10/14/ the-value-of-pollinators-to-the-ecosystem-and-our-economy/?sh=d4ca0b7a1d65 [4] Abbott, C. (2020, August 4). Colony collapse toll is highest in four years for U.S. honeybees. Successful Farming. Retrieved March 29, 2021, from https://www.agriculture. com/news/livestock/colony-collapse-toll-is-highest-in-fouryears-for-us-honeybees [5] Coldewey, D. (2020, May 28). BeeHero smartens up hives to provide ‘pollination as a service’ with $4M seed round. TechCrunch. Retrieved March 29, 2021, from https:// techcrunch.com/2020/05/28beehero-smartens-up-hivesto-provide-pollination-as-a-service-with-4m-seed-round/

science cocktail REFERENCES 12

How Tiny Nanoparticles Help Us Fight Big Problems Written by Ethan Feng Illustrated by Lizka Vaintrob

In recent years, developments in nanotechnology— and in particular, nanoparticles—have been thrust into public discourse and popular culture. Most recognizably, perhaps, Tony Stark donned armor composed of nanotechnology to defeat Thanos and save the universe in the grand finale of Marvel’s Infinity Saga. However, while these depictions are certainly thrilling, the concept of nanoparticles has become increasingly muddled and loosely interpreted, to the point that it may be difficult to distinguish facts from imagination. So, one might wonder, what are real-life nanoparticles, and what are they actually capable of?

Basic Principles First, let us start by defining what “nanoparticle” really means. The prefix “nano” generally refers to objects that are roughly 1 to 100 nanometers (nm) in size.1 To put that into perspective, imagine taking the width of a single human hair and dividing it by one hundred, then by one hundred again! It is objects at this tiny scale that qualify as “nano.” On top of this, every object has three dimensions—think length, width, and height—and anywhere between zero and all three of these dimensions can be at the nanoscale. For example, most everyday objects have no dimensions in the nanoscale; a very thin sheet, called a nanosheet, has just one dimension in the nanoscale (its thickness); and a very thin wire, called a nanowire, has two dimensions in the nanoscale but a third dimension at a larger scale. In the most general sense, nanoparticles can be defined as matter for which all three dimensions are in the nanoscale. This makes them so small that most nanoparticles are just clusters of a couple hundred atoms! 1 One nanometer is one billionth of a meter.

Figure 1: An example of platinum (left) and gold (right) nanoparticles synthesized in a lab. The particles are suspended in a solvent (organic solvent and water, respectively).

Under this quite broad definition, nanoparticles can take many forms and can be composed of all kinds of different materials: common materials range from metals such as platinum and gold, to oxides like alumina and silica, to even organic compounds, as we will see later in this article. While they are most often spherical, researchers are capable of synthesizing nanoparticles of countless different shapes, including cubes, pyramids, and even stars. Furthermore, although it is common to picture nanoparticles as a tiny solid grainy material (many initially think of sand), this is not the case. In reality, perhaps counterintuitively, nanoparticles are usually housed in a liquid solvent or attached to some larger solid structure, as they are not stable on their own. Due to their smallness, nanoparticles approach the size regime where matter is governed by quantum mechanics, giving rise to a myriad of unusual and fascinating properties that differ from their larger bulk-matter counterparts, including optical, electronic, magnetic, and catalytic properties. For example, because nanoparticles are smaller than the typical wavelength of visible light (~400-700 nm), they interact with light in an unusual way, causing some metal nanoparticles to have unexpectedly vibrant colors. Humans have harnessed these unusual properties of nanoparticles since Greco-Roman antiquity: famously, early artisans incorporated gold nanoparticles into their stained glass works, due to the particles’ distinctive vibrant red color (although they likely had little understanding of what they were working with) [1, 2]. The first rigorous characterization of nanoparticles was pioneered by renowned chemist Michael Faraday in the mid-1800s, but it was not until recent decades that research in nanoscience has rapidly expanded. By now, scientists have thoroughly investigated the nature of nanoparticles and have techniques that allow them to precisely design nanoparticles as desired. They can tune the size, composition, and shape of the particles and can also attach other smaller molecules to their surface as necessary to fit the intended application. Now, let us delve into some of the most promising of such applications.

Applications in Green Chemistry Climate change is arguably the most pressing crisis of the modern world. Carbon-based greenhouse gases emitted into the atmosphere in enormous quantities prevent the sun’s heat from escaping, leading to rapidly increasing temperatures, and in turn, detrimental consequences across the globe. Needless to say, humanity must take swift and drastic action to reduce greenhouse gas emissions before the damage becomes irreversible. You probably already knew this. Here’s what is not as commonly known: Although carbon dioxide (CO2) is often painted as the main villain of this crisis by public discourse, CO2 is actually a relatively mild greenhouse gas. While it is true that CO2 emitted into the atmosphere is responsible for a large portion of the greenhouse effect (and it is absolutely a problem to be addressed), this is mostly just because we release it in such large amounts. However, on a pound-for-pound basis, many other commonly emitted gases—especially methane, propane, and other hydrocarbons—are up to 100 times more potent heat-trappers than CO2 and are much worse for the environment [3]. This means that if we have devices that tend to emit these hydrocarbon gases—car engines, for example, produce them as a byproduct—it would be advantageous to convert the hydrocarbons into CO2 and to emit CO2 instead. Obviously, emitting CO2 is still bad, but it is less bad than emitting hydrocarbons, so such a conversion would result in a net environmental benefit. So, our goal is to convert hydrocarbons to CO2. We can do this via a simple reaction known as combustion, which involves mixing hydrocarbons with oxygen to produce CO2 and water. This is what happens when you, for example, burn wood. While this sounds simple on paper, in reality, unfortunately, performing this reaction as stated requires very high temperatures and enormous energy input. Not only is this unsafe in practical settings (e.g., in a car), but seeing as the basic goal in fighting climate change is to reduce energy usage, requiring high energy input for this process would defeat its purpose. Fortunately, there is a solution: a catalyst. A catalyst is a material that, when added to a reaction, lowers the energy input required without altering the initial or final states of the reaction. It does so by interacting with the reactants to provide an alternate, lower-energy chemical mechanism for the reaction. By adding a catalyst, hydrocarbons can be converted into CO2 with a much smaller energy penalty.

As it turns out, researchers have found that several transition metal elements—including palladium, platinum, ruthenium, and more—are excellent catalysts for the combustion reaction of interest [4]. These metals interact with the hydrocarbon gas in a particular way that makes the reaction with oxygen much easier. The fact that these catalysts are metals, however, introduces a new wrinkle: for the catalyst to do its job, it must be able to actually come into contact with the hydrocarbon gas. If we had two gases or two liquids, it would be relatively simple to bring them in contact—just mix them. But in our case, the catalyst is a metal—i.e., a solid—while the hydrocarbon and oxygen are gases; such a scenario, where the catalyst and reactants are in different phases, is known as heterogeneous catalysis. One cannot simply mix a solid with a gas to increase contact, since the gas cannot easily penetrate the solid. This means that the only place in which the gas can interact with the metal catalyst is on the metal’s surface. To maximize the catalyst’s efficacy, we want as much interaction with the hydrocarbon and oxygen gases as possible; so, the goal now becomes to maximize the surface area of metal per amount of metal catalyst. The natural solution is to split a given amount of metal catalyst into very many, very small pieces (as opposed to one large piece). To illustrate why, imagine a Rubik’s cube: Initially, for the single, undivided cube, the only surfaces exposed are the colorful squares on the outside of the cube. But now, imagine breaking off each of the smaller cubes that compose each face—as you separate more of the smaller cubes, the blank surfaces on the inside of the Rubik’s cube now become exposed, hence increasing the surface area! This basic illustration shows why many small metal particles have greater surface area, and in turn better catalytic efficacy, than one large particle with an equal mass of metal. (A single chunk of metal is indeed a mediocre catalyst.) Take this to the extreme, making the catalyst as small as it can get, and we conclude that nanoparticles are the optimal configuration of the catalyst! Unfortunately, nature dislikes small things. When many tiny nanoparticles are near each other, they have a strong tendency to agglomerate, in many ways similar to how small water droplets naturally form into one bigger drop when placed into contact with each other. But based on the ex-

planation above, particle agglomeration is exactly what we do not want, since it reduces the surface area. So, how can we prevent this? The solution is to use a support material: a larger, inert material to which the catalytic nanoparticles can be attached (alumina and silica are common choices). Tethering the nanoparticles to the support makes them unable to move around as much, thus preventing them from coming into contact and agglomerating. 1

Figure 2: A real-life image of metal nanoparticles bound to a support material. The large chunk is the support, while the small black dots are the nanoparticles. For scale, the white line in the bottom-right corner represents 100 nm. With this nanoparticle-support material combination in hand, we have the ultimate tool to prevent the emission of harmful hydrocarbon gases. To elaborate upon an example mentioned earlier, we can revisit a common application of this in cars: automotive engines release hydrocarbons as byproducts, and it is environmentally advantageous to convert them to and emit an equivalent amount of CO2 instead. To achieve this, a device called a catalytic converter, which usually contains platinum nanoparticles, is placed in between the car engine and the end of the exhaust pipe. As the hydrocarbon byproduct exits the engine, it passes through the catalytic converter and reacts into CO2, which is then released, ensuring that the harmful hydrocarbons are never emitted in the first place. 1 It is true that this attachment may take up some fraction of the nanoparticle’s surface, thus decreasing the surface area accessible to the gaseous reactants. However, this slight cost is greatly outweighed by the benefit of preventing agglomeration.

Although this article has primarily introduced these concepts through the lens of preventing hydrocarbon emissions, supported metal nanoparticle catalysts are also used to heterogeneously catalyze a wide variety of similar gas-phase reactions. To name a few, these include converting harmful NO, NO2, and CO byproducts from car engines into CO2 and N2 as well as synthesizing ammonia (NH3) from nitrogen and hydrogen more efficiently, which is crucial in agriculture. The rationale behind all these applications is the same: in a gaseous reaction, smaller metal particles are better catalysts thanks to their greater surface area. While this technology is indeed an immense tool in the fight against greenhouse gas emissions, as with any technology, it has its drawbacks. For instance, although the support material helps to stop the nanoparticles from moving and agglomerating, it is not foolproof. At high temperatures, such as those generated by a car engine, some nanoparticles may gain enough energy to break their bond to the support material, migrate, and agglomerate. Because of this, the catalyst can degrade and lose efficiency over time, especially after repeated use. Researchers are currently trying to find methods to overcome this: one of the more exciting ideas is to build a microscopic cage around each nanoparticle, with holes small enough to prevent agglomeration but large enough to still let in the gaseous reactant molecules [5]. Another practical concern is that some of these metals, such as platinum, are very expensive. Consequently, scientists are experimenting with different materials to find more cost-effective catalysts that can give the “same bang for less buck.” Because all the catalysis takes place on the surface of the particles, the composition of the center of the particles is less important; so, researchers have developed “core-shell” nanoparticles, whose interior is composed of an inexpensive material while the exterior surface is coated with the expensive catalytically active metal, thus reducing costs while maintaining high catalytic efficacy [6]. Ultimately, researchers remain hard at work to develop the best catalysts in the looming battle against climate change.

Applications in Drug Delivery Let us change gears from a very large-scale problem to a smaller-scale, yet equally dangerous crisis: cancer. Striking nearly 40 percent of all humans at some point in life [7], cancer is among the most deadly diseases—and to make matters worse, it is difficult to treat. While drug-based treatments such as chemotherapy are widely used, they often cause detrimental side effects and have a suboptimal success rate. How can drugs be improved to yield better results? There are two main problems with traditional drug delivery methods—let us explore them one by one: i. Minimizing Drug Dosage In drug design, a common principle is to try to minimize the dosage needed to achieve the desired effects, so as to minimize adverse disturbances to the body. Unfortunately, there is one factor that gets in the way of this goal: traditionally, when a drug is administered, most of the dose never even makes it to the target site. Suppose for example that a patient takes a drug via the mouth intended to treat a tumor elsewhere in the body. After the drug is ingested, before it can have any beneficial effects, it must arrive at the tumor first. However, during the journey there, the drug faces many obstacles. First, the body recognizes the drug as a foreign substance and thinks it is dangerous, so it immediately sends enzymes in the bloodstream to destroy the drug; the liver is also programmed to rid the body of any substances that it views as harmful. Additionally, as it passes through the stomach, much of the dose gets degraded by the stomach acids. Moreover, once the drug is in the intestine, where it must be absorbed, it has a hard time passing through the intestinal wall, which has highly selective permeability. Due to all these factors, by the time the drug reaches the tumor, most of it will have been lost already [8]. To compensate for this loss and to ensure that an adequate amount of drug makes it to the target site, the dose usually needs to be quite large, which is problematic since it directly opposes the initial goal of minimizing the dosage.

If the problem is the drug being degraded during its journey, then the solution is to protect it. Scientists have developed a type of hollow nanoparticles called liposomes, whose surface is made of a phospholipid bilayer, the same substance that composes the membrane of cells. Drug molecules can then be encapsulated inside of these hollow nanoparticles, which shield the drug molecules from danger. Think of these liposomes as the bubble wrap that protects your online purchase during its journey through the mail to you. As the nanoparticle-encapsulated drug enters the body, like before, the body sends enzymes to destroy the drug molecules, but the nanoparticles shield them from the enzymes, leaving them fully intact. Similarly, the nanoparticles are resistant to the stomach’s acids, allowing the drug to pass through relatively unscathed [9]. Moreover, although the intestinal permeability is highly selective, the fatty composition of the nanoparticles fortunately allows them to pass through easily [10]. Once the nanoparticles arrive at the target site, because they are made of the same material as cells’ membranes, cells can easily absorb them, along with the drug. Altogether, the nanoparticle encapsulation means a much greater fraction of the original dose makes it to the target site, thus reducing the dosage needed and, consequently, the adverse side effects. ii. Increasing Drug Selectivity However, after the drug makes it safely to the target site, the fight is not yet over. A second key principle in drug design is that the drug should be as selective as possible—that is, it should only attack sick cells, leaving healthy cells alone as much as possible. Unfortunately, without any additional tools, the drug has a hard time distinguishing between healthy and sick cells, and as a result, may attack perfectly healthy cells. For example, the unpleasant side effects of chemotherapy, such as hair loss and nausea, are a consequence of this problem. How can we increase drug selectivity to prevent this?

The detail crucial to the solution is this: cells’ surfaces are covered with various proteins that act as “locks,” and only entities with the correct “key” can enter into the cell. Moreover, sick cells often develop different lock proteins than healthy cells. We can take advantage of this fact: through precise engineering, scientists can attach the specific key protein that corresponds to sick cells onto the surface of the nanoparticles that carry the drug. By doing this, the liposomes specifically target only the sick cells, thus reducing the number of negatively affected healthy cells [11]! To recap, by encapsulating the drug inside of liposomes whose surfaces contain proteins that specifically lock in on diseased cells, we can both reduce the drug dose needed and the harmful side effects. While this nanoparticle-based drug delivery system is still in development, it is already being harnessed to treat cancer, as well as many other diseases beyond, showing great promise in many different areas.

Figure 3: A simplified computer illustration of a liposome. The blue and yellow represent the phospholipid bilayer, while the red and green represent the drugs encapsulated within the particle.

In fact, these nanoparticles may be closer to you than you might realize. To give one final example of their relevance, liposomes play an integral role in the newly developed COVID-19 mRNA vaccines: the key component of the vaccine, the viral mRNA (essentially the virus’s genetic material), is recognized by the body as foreign, so the body attacks it; furthermore, the structural properties of mRNA make it difficult for it to enter into cells on its own. Thus, delivering bare viral mRNA to cells is infeasible. Scientists overcame this problem by encapsulating and protecting the viral mRNA in liposomes, hence drastically increasing the efficiency of its delivery into cells [12]. Clearly, nanoparticles can help us solve even the most daunting of problems, and this will only continue as nanotechnology advances.

REFERENCES [1] Daw, R. (2012, April 24). Nanotechnology is ancient history. The Guardian. https://www.theguardian.com/nanotechnology-world/nanotechnology-is-ancient-history#:~:text=In%20 the%20antiquities%2C%20nanoparticles%20were,Romans%20 to%20craft%20iridescent%20glassware.&text=The%20stunning%20Lycurgus%20cup%20reveals,containing%20gold%2Dsilver%20alloyed%20nanoparticles [2] Chan, C. (2008, June 22). From nanotech to nanoscience. Science History Institute. https://www.sciencehistory.org/distillations/from-nanotech-to-nanoscience [3] Myhre, G., Shindell, D., Bréon, F.-M., Collins, W., Fuglestvedt, J., Huang, J., ... & Zhang, H. (2014). Anthropogenic and natural radiative forcing. Climate change 2013: The physical science basis. Contribution of working group I to the fifth assessment report of the intergovernmental panel on climate change (pp. 659-740). Cambridge University Press. [4] Liu, L., & Corma, A. (2018). Metal catalysts for heterogeneous catalysis: From single atoms to nanoclusters and nanoparticles. Chemical Reviews, 118(10), 4981-5079. [5] Sun, J., Zhan, W., Akita, T., & Xu, Q. (2015). Toward Homogenization of Heterogeneous Metal Nanoparticle Catalysts with Enhanced Catalytic Performance: Soluble Porous Organic Cage

as a Stabilizer and Homogenizer. Journal of the American Chemical Society, 137(22), 7063–7066. [6] Zaleska-Medynska, A., Marchelek, M., Diak, M., & Grabowska, E. (2016). Noble metal-based bimetallic nanoparticles: the effect of the structure on the optical, catalytic and photocatalytic properties. Advances in Colloids and Interface Science, 229, 80-107. [7] Cancer Statistics. (2020, September 25). National Cancer Institute. https://www.cancer.gov/about-cancer/understanding/statistics [8] Tedx Talks. (2015, July 1). Nanoscience and drug delivery [Video]. YouTube. https://www.youtube.com/watch?v=0wFwXUhHu5c [9] Ball, R. L., Bajaj, P., & Whitehead, K. A. (2018). Oral delivery of siRNA lipid nanoparticles: fate in the GI tract. Scientific Reports, 8(1), 1-12. [10] He, H., Lu, Y., Qi, J., Zhu, Q., Chen, Z., & Wu, W. (2019). Adapting liposomes for oral drug delivery. Acta Pharmaceutica Sinica B, 9(1), 36-48. [11] Riaz, M. K., Riaz, M. A., Zhang, X., Lin, C., Wong, K. H., Chen, X., ... & Yang, Z. (2018). Surface functionalization and targeting strategies of liposomes in solid tumor therapy: A review. International Journal of Molecular Sciences, 19(1), 195. Cross, R. (2021, March 6). Without these lipid shells, there would be no mRNA vaccines for COVID-19. Chemical & Engineering News. https://cen.acs.org/pharmaceuticals/drug-delivery/ Without-lipid-shells-mRNA-vaccines/99/i8 [12] Nune, S. K., Gunda, P., Thallapally, P. K., Lin, Y. Y., Laird Forrest, M., & Berkland, C. J. (2009). Nanoparticles for biomedical imaging. Expert Opinion on Drug Delivery, 6(11), 1175-1194. [13] Moynihan, T. (2015, January 19). What are quantum dots, and why do I want them in my TV? Wired. https://www.wired. com/2015/01/primer-quantum-dot/ Figure References [1] (Left) My own image. (Right) Mohandas, N. (2020, July 25). A Nano-tale of the Vivid Colours of Gold. Research Matters. https://researchmatters.in/ sciqs/nano-tale-vivid-colours-gold [2] Zhou, J., Huang, Y., Shen, J., & Liu, X. (2021). Pd/C-Catalyzed H 2 Evolution from Tetrahydroxydiboron Hydrolysis. Catalysis Letters, 1-7. [3] Baumber, M. (2020, June 24). Training on Creating Liposome-based Drug Delivery Systems. Microfluidics. https://www. microfluidics-mpt.com/blog/webcast-training-on-creating-liposome-based-drug-delivery-systems

Written By Victoria Comunale Illustrated by Vanshika Siriam

ALLERGIES 20

The air we breathe, the food we eat, and the things we touch all characterize essential interactions with the world around us. Not only are many of our actions vital to our survival, but many also enrich our experiences on Earth. Our senses allow us to have a conversation with our immediate environment and enable us to feel sensations such as happiness in response to eating our favorite meal or after smelling fresh flowers. However, while a certain meal or fresh flowers may bring joy to some, in others it can induce itchy discomfort or possibly life-threatening conditions brought about by allergic reactions. Allergies are one of the most common chronic conditions: it is estimated that over 50 million people are affected in the United States alone [1]. Allergies can be mild, causing only slight discomfort, or they can be extremely severe, leading to intense swelling and even the possibility of death. As we grow more aware of how allergies work, evidence also shows that they are becoming more prevalent [1]. Why do some people experience allergic reactions when exposed to certain substances and environments? Allergies occur in response to one’s immune system mis-identifying harmless substances as incredibly harmful pathogens [2]. Peanuts, pollen, and bee venom are common allergens—substances that provoke allergic reactions [1]. Understanding the mechanism of the immune system affords us a greater glimpse as to why allergic reactions may occur. When threatening microbes make it into your body, the B and T cells of your immune system play a large role in identifying them and initiating a plan of attack [2]. B cells have proteins, known as antibodies, located on their membranes. These antibodies bind to antigens, which are foreign pathogens or substances that are perceived as dangerous, marking them to be destroyed by the rest of the immune system. T cells also play important roles in the immune response. T cells both help destroy in-

fected cells and stimulate B cells to make more free-floating antibodies[2]. Some B cells which can produce the correct antibodies are also induced to become memory cells. This allows for a faster attack when the foreign substance is reintroduced into one’s body. In the case of allergies, when your body is exposed to the allergen in the future, there will be an immediate and concentrated immune response. This is associated with the release of many chemicals such as histamine. The release of these chemicals elicits a response from other cells and tissues in your body. One such response is an increase in blood flow to the site of the allergen. Blood vessels become leakier and more dilated, and your body increases mucus production as well [2]. These responses lead to the common symptoms of swelling and redness that are normally associated with allergic reactions. However, some reactions can be life-threatening if the dilation and leakiness of the blood vessels become too severe, as in the case of anaphylactic shock. During such a shock, too much blood being diverted to the affected site can cause low blood pressure, allowing less blood flow to vital organs. Furthermore, the anaphylactic response also leads to muscle contractions around the lungs, not only preventing adequate amounts of oxygen from entering your body, but also reducing overall blood flow, both of which are equally dangerous [2]. There are many theories as to why allergies exist, and much research is being done to investigate such theories due to the increasing prevalence of people developing allergies. In the United Kingdom specifically, a recent study in 2016 found that children were developing peanut allergies at a rate five times higher than children were in 1995 [3]. Overall, seven percent of children in the United Kingdom were found to have food allergies [3], and data reporting overall allergy prevalence in children from ages 0-18 in 2013 found that the United Kingdom ranked the highest, with Finland, Lithuania, and the United States close by [4]. One leading theory is that the environment in which a person is raised plays an important role in the development of allergies. Places with overall less allergen levels may counter-

intuitively cause people to have a greater sensitivity to such allergens. This is because the immune system’s mechanisms are not as often employed, and so it may have less specificity and more room for error as to what it identifies as microbes. With the lack of harmful pathogens, the body could turn to substances that should be benign. The environmental influence of allergies was further explored in a study from 2016, which compared the incidence of allergies between immigrants and non-immigrants in Canada. After analyzing the data of over 100,000 individuals that responded to the Canadian Community Health Survey, the researchers found that recent immigrants were only a third as likely to have allergies as non-immigrants were, suggesting that the environment one is brought up in has a strong influence on the development of allergies [5]. However, this is not a definitive answer to how allergies develop, and much more data must be collected before such an answer is reached. The relative amount of amassed data is vastly different for different regions - European and North American countries dominate in terms of data collected about the development of allergies [4]. In largely rural countries, reduced medical infrastructure limits the recognition and documentation of allergy prevalence. Furthermore, since allergies come in different forms and magnitudes, it is difficult to adequately categorize them. Allergies can be as simple as mild discomfort to as severe as anaphylaxis; however, medical intervention is typically provided only for the more noticeable and uncomfortable allergies.

There currently exists no cure for allergies, although antihistamines and epinephrine have proven to be effective modes of medical intervention [1]. Deaths still occur due to anaphylactic shock, and could continue to rise along with the increased frequency of allergies [3]. However, there is hope that severe allergic reactions could become more controllable in the future. A recent immunotherapeutic trial targeted people who are extremely allergic to peanuts, administering small doses of peanut protein to one group and a placebo to another every day for 24 weeks [6]. After the time period, the majority of participants who received the peanut protein were able to tolerate ingesting two peanut kernels while only 4 percent of the control group were able to do the same. Methods like these, although not a cure for allergic reactions, can help lessen the severity of one. While much is still unknown about allergies, we are slowly finding methods of combating allergic reactions in the hopes of eliminating them altogether. What still stands as a significant piece of the puzzle is how they arise and what causes them. We can hope to answer this question through increasing the scope of our data regarding allergy development around the world, creating more therapeutic methods, and progressing research to demystify what goes on beneath the surface.

References [1] Allergy Statistics in the US. (2021, January 21). Retrieved from https://allergyasthmanetwork.org/ allergies/allergy-statistics/ [2] Vickery, B. P., Chin, S., & Burks, A. W. (2011, April). Pathophysiology of food allergy. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/ PMC3070117/ [3] Santos, D. A. (2019, September 13). Why the world is becoming more allergic to food. Retrieved from https://www.bbc.com/news/ health-46302780#:~:text=The increase in allergies is,of allergies in developing countries [4] SL. Prescott, K. A., LM. Poulos, A. W., NJ. Osborne, J. K., TF. Leung, E. Y., MI. Asher, S. M., N. Ait-Khaled, N. P., . . . JM. Skripak, E. M. (1970, January 01). A global survey of changing patterns of food allergy burden in children. Retrieved from https://waojournal.biomedcentral.com/articles/10.1186/1939-4551-6-21 [5] Cabieses, B., Uphoff, E., Pinart, M., Antó, J. M., & Wright, J. (2014, August 20). A systematic review on the development of asthma and allergic diseases in relation to international immigration: The leading role of the environment confirmed. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/ PMC4139367/ [6] The PALISADE Group of Clinical Investigators, Perkin, M., K. G. Blumenthal and Others, & Others, N. D. (2018, November 22). AR101 Oral Immunotherapy for Peanut Allergy: NEJM. Retrieved from https://www.nejm.org/doi/full/10.1056/NEJMoa1812856?query=featured_home

Whether it be the flat Earth theory or religious radicalism, social media platforms have allowed dangerous, false ideas to reach millions of users. Because companies like Facebook profit from advertising, they design their algorithms to keep people online. They harvest our behavioral data to predict our next digital steps. Polarizing and false messages attract more online viewership than objective, accurate content. Thus, social media algorithms promote conspiracy theories and extremism to make their users see more ads. Exposure aside, how do normal people like you and me come to embrace these ideologies? How do people center their identities around unevidenced ideas? How do people’s beliefs compel them to act violently? The answer lies in brainwashing, the systematic targeting of noncompliant or unsuspecting people with the aim of reconstructing their identities and worldviews. Its ultimate goal is to control the behaviors and thoughts of the target [1]. By this logic, all lawyers, politicians, and parents could be considered brainwashers. However, a key distinction between normal authority and brainwashers lies in the method of instilling beliefs. Psychiatrist Robert Lifton’s eight criteria of thought reform show up in varying capacities in instances of brainwashing [2]: (1) Milieu Control entails the isolation of an individual from greater society. The subject’s access and communication to the outside world is strictly monitored. (2) Mystical Manipulation occurs when a brainwasher claims divine or spiritual authority to portray a set of events the way they want.

Many religious cult leaders have employed this tactic to legitimize their ideology. (3) Demand for Purity divides group members and outsiders into two groups: pure and impure, respectively. People who believe in the group’s messages are pure, those who think differently are dirty. The group must separate themselves from the outsiders to prevent their minds from being tainted. (4) Cult of Confession is the loss of individual privacy. A person surrenders themselves to the group, confessing their “impurities.” By removing these boundaries, the group symbolically owns the individual. (5) Sacred Science is when a group proclaims its dogma to be morally unchallengeable. Group members are not allowed to question the group’s beliefs. (6) Loading the language is another effective brainwashing tactic wherein complex ideas, usually concerning humanity’s most pressing problems, are concentrated into short, definitive phrases. Such slogans are referred to as “thought-terminating,” decreasing an individual’s critical thinking upon being heard. (7) Primacy of doctrine over person subjugates the human experience to the doctrine of the group. Historical events may be rewritten to align with the doctrine. The doctrine supersedes every aspect of humanity: character, memory, experience, and beliefs. (8) The Dispensing of Existence declares that the group leader/ doctrine controls the lives and fate of its group members. This method of brainwashing has had violent repercussions, such as the 1978 Jonestown mass murder-suicide.

BELIEVE BELIEVE ME ME Written by Shivani Tripathi Illustrated by Nicole Lin

There are prominent signs which indicate whether someone has been brainwashed or not. A short time of transition between old and new beliefs fundamental to one’s identity suggests that brainwashing has occurred. Let’s say an atheist becomes deeply religious within the timespan of a week. Such a drastic change in one’s worldview may imply the external influence of brainwashing. However, if that person had changed their mindset over the course of a few years, it was more likely a natural process. Another sign of brainwashing is when group members give hyper-emotional responses when their beliefs are criticized. For instance, studies show that cult members refuse to engage in fact-based, logical debates about their beliefs [1]. Brainwashing occurs not only on a psychological level but also on a biological level. In general, mental activities are represented by highly changeable patterns of connections between neurons in the brain. Neurons are nerve cells that transport information throughout the body through electrical and chemical signals. Most do not physically touch at the site of information transfer, but instead transmit signals across the space between cells, which is called a synapse [3]. In the receiving neuron, these electrical signals trigger the release of neurotransmitters, chemical substances made by a neuron to communicate a message. Some of the neurotransmitters localize to receptors on the next neuron’s surface, causing this receptor to change shape, either allowing or activating proteins that allow certain molecules to flow across the cell membrane through gates. Such a flow changes the electrical voltage of the cell and potentially triggers secondary signals. Eventually, the neurotransmitter detaches from the receiving molecule and the receptor returns to its passive state [4]. However, the repeated insertion of transmitter molecules can cause long-lasting changes to a cell’s genetic

machinery. Moreover, the more frequent or intense an incoming signal is to some neurons, the stronger the connections between those neurons will become [1]. Gradually, our brain groups our neural patterns into schemas and beliefs. A schema is a cognitive framework that we develop to regulate our intake of information. Schemas provide shortcuts in organizing the information in our environment, and different schemas are activated for different social situations. In neuroscience, schemas can be represented by the simultaneous activation of a group of neurons. A given neuron fires off signals in response to an input. The input includes the features of an object, such as color, sound, and movement. Representing an entire object requires the simultaneous activation of a group of connected neurons. Schemas can be placed on a spectrum from weak to strong. Weak schemas are not used frequently and may require a conscious effort to employ. The strengths of their connections are low, and any change to a weak schema would not affect one’s sense of self. On the other hand, strong schemas have

very strong connections between their networks of neurons. The connections are difficult to change, and if they do change, one’s identity could be severely impacted [1]. Our brain also groups neural patterns into beliefs. While schemas enable us to perceive our surroundings, beliefs are how we interpret these surroundings. Beliefs are as strong as the connections between their components: neuron interactions and the brain’s interactions with the outside world. In other words, we’ve developed neural patterns which have a preordained response to certain inputs. Beliefs and schemas can be collectively referred to as cognitive-webs (cogwebs). Cogwebs range from higher order beliefs to basic functions such as walking and eating [1]. A brainwasher must overcome a person’s higher order cogwebs in order to brainwash them. The stronger a person’s cogwebs are, the more difficult it is to do so. For example, an advertisement could immediately influence your opinion about something not that important to you, like goldfish. But it would take a lot more convincing to change your opinion on your spouse, who you’ve spent years analyzing [1]. Our bodies have defenses against brainwashing, the first being the condition of our cogwebs. Strong cogwebs are less prone to being altered. Signals flow through the brain by way of cogwebs already present. If the match between the new input and current brain structure is poor, there will be little information flow through available cogwebs. Either the cogwebs will adjust, or new cogwebs will form to carry away the surplus. The other option is that input signals will be modified to better fit the brain’s expectations. The outcome depends on the connection strengths of the cogwebs activated. In the case of stronger cogwebs, expectation often supersedes reality. Weaker cogwebs are more likely to adjust to accommodate the unfamiliar input. However, stronger cogwebs lead to more input change. Thus, our brains are unreceptive towards information that challenges our strong cogwebs [1]. The unwillingness for our strongest cogwebs to adapt to new information could manifest in confirmation bias. The partisan divide over which media outlets voters trust may be a prime example. According to Pew Research, 70 percent of Democrats trust CNN, a liberal news outlet. On the flip side, the majority of Republicans (67 percent) distrust CNN. A similar disparity is evident concerning Fox News, a conservative outlet. 75 percent of Republicans trust Fox News, while 77 percent of Democrats distrust Fox News [5]. Challenging our strong cogwebs is a difficult task, which could explain why people seek environments which align with their ideological comfort zones.

Cogweb density is another defense mechanism against brainwashing. The denser your cogweb landscape, the more cogwebs you have. When a cogweb in a dense area of your brain is activated, it may also activate nearby cogwebs, enabling you to draw upon a multitude of thoughts and experiences to interpret stimuli. People with vast cognitive landscapes may be more flexible when it comes to processing stimuli. A higher degree of education, experiences, and memories may enable people to think critically about the information presented [1]. Rich cognitive landscapes also equip one to defend against emotional attacks. For example, children are easier to brainwash than adults because the latter have more emotional maturity and knowledge to see through the manipulation [1]. Cogweb simplicity is a key defense as well. Simple stimuli are more likely to evoke faster responses than more complicated stimuli. The simplest stimuli can evoke such a rapid response that there is no time for other parts of the brain to even realize that the stimulus has occurred. Simpler beliefs are harder to challenge because their cogwebs are activated without even reaching conscious awareness. Therefore, our strongest beliefs will have simpler, more succinct cogwebs than our weaker beliefs. Simple cogwebs enable ever-present, subconscious reactions to stimuluses, greatly impacting behavior and identity [1]. In addition to the condition of our cogwebs, the stop and think function is a vital inhibitor of brainwashing. The stop and think function is when people decide whether to accept new information or not. A brainwasher must overcome their victim’s ability to reject ideas by bombarding the prefrontal cortex. The prefrontal cortex is the anterior portion of the brain’s frontal lobe. The region is responsible for complex cognitive behavior, such as decision-making and socializing [6]. The prefrontal cortex is most active when dealing with novel ideas. As a result, the introduction of unfamiliar information causes intense, taxing prefrontal cortex activity. Brainwashers abuse their victims’ prefrontal cortexes by inflicting intense emotions, thereby inhibiting the stop and think function. When we experience anger, sadness, or fear, our ability to “stop and think” is obstructed. It becomes more difficult to think critically and draw upon past knowledge and experiences. We act and think in a more impulsive manner. In some cases, this could lead to strong cogwebs being fundamentally altered and new cogwebs being accepted. Victims eventually realise that adopting the brainwasher’s beliefs is the only way to relieve their prefrontal cortex from over stimulation [1]. In some cases, over stimulation is explicit. When brainwashing by force, perpetrators employ beatings, insults, starvation, and other forms of abuse to overcome their target’s stop and think function. Brainwashing by stealth is more subtle, but also uses emotions to

overwhelm the prefrontal cortex. For example, spreading conspiracy theories on social media could be considered a way of brainwashing by stealth. After exposing targets to inaccurate information, algorithms control what their users perceive. When an algorithm detects you engaging with a certain type of content, it will fill your feed with posts of a similar nature to keep you online. Former Facebook Executive Officer Chamath Palihapitiya put it this way: “We want to psychologically figure out how to manipulate you as fast as possible and give you back that dopamine hit” [7].

substance abuse inhibit critical thinking [1]. Engaging in self-care and stimulating our neurons with new experiences and education could prepare us to resist the charisma of the next stealthy despot.

Repeated exposure to fake news desensitizes users to ideas they would have once considered ludicrous. Furthermore, fake news tends to be polarizing and emotionally charged, potentially interfering with a user’s ability to stop and think. Such posts induce fear, anger, apprehension, and stress—emotions which may inhibit people’s capacity to stop and think.

[1] Taylor, K. E. (2004). Brainwashing: The science of thought control. Oxford: Oxford University Press. [2] Martin, P. (2003, February 12). Robert Jay Lifton’s eight criteria of thought reform as applied to the Executive Success Programs. Retrieved April 4, 2021, from https://www.cs.cmu. edu/~dst/NXIVM/esp11.html [3] Britannica, T. Editors of Encyclopaedia (2020, November 30). Neuron. Encyclopedia Britannica. https://www.britannica.com/ science/neuron [4] Britannica, T. Editors of Encyclopaedia (2020, May 28). Neurotransmitter. Encyclopedia Britannica. https://www.britannica. com/science/neurotransmitter [5] Shearer, E. (2021, January 12). 86% of Americans get news online from smartphone, computer or tablet. Retrieved April 4, 2021, from https://www.pewresearch.org/facttank/2021/01/12/more-than-eight-in-ten-americans-getnews-from-digital-devices/ [6]Morecraft, R., Yeterian, E., (2002) Prefrontal Cortex. Editor(s): V.S. Ramachandran, Encyclopedia of the Human Brain, Academic Press, (11-26) https://doi.org/10.1016/B0-12-227210-2/00285-5. (https://www.sciencedirect.com/science/article/pii/ B0122272102002855) [7]Orlowski, Jeff, director. The Social Dilemma. Netflix Official Site, Netflix, 2020, www.netflix.com/watch/81254224?trackId=13752289. [8]Mark Jurkowitz, A. M. (2020, August 28). U.S. Media Polarization and the 2020 Election: A Nation Divided. Retrieved April 4, 2021, from https://www.journalism.org/2020/01/24/u-smedia-polarization-and-the-2020-election-a-nation-divided/ [9]Rosen, G. (2021, March 22). How We’re Tackling Misinformation Across Our Apps. Retrieved April 4, 2021, from https:// about.fb.com/news/2021/03/how-were-tackling-misinformation-across-our-apps/ [10] Jackson, J., Heal, A., & Wall, T. (2021, April 11). Facebook ‘still too slow to act on groups profiting from Covid conspiracy theories’. Retrieved April 12, 2021, from https://www.theguardian.com/technology/2021/apr/11/facebook-still-too-slow-toact-on-groups-profiting-from-covid-conspiracy-theories

The increasingly widespread acceptance of inaccurate information has had a polarizing effect on society. First of all, social media has immersed different users in different realities. Algorithms build your feeds based on your location and past activity [7], and so digital echo chambers are constructed—echo chambers which encourage intolerance and polarization in real life. Because fifty-seven percent of Americans get news from social media [8], we may erroneously believe that everyone agrees with us due to our online presence. So when we see people disagreeing with us in real life, many of us may look down upon them with a sense of self-righteousness, wondering why they don’t just accept the facts. Well, the algorithms have ensured that different people have different facts [7]. Social media companies have a societal responsibility to combat misinformation. For example, Facebook has disabled over a billion fake accounts. It has hired fact-checkers to review widely circulated content and has also built systems to remove “inauthentic” and “deceptive” behavior [9]. However, recent investigations have shown that Facebook is still profiting off of misinformation concerning vaccines and the coronavirus pandemic [10]. Moreover, fake news on Twitter spreads six times faster than real news [7]. Hence, although companies are taking action, they are fundamentally incentivized not to. Users must remain vigilant when encountering information on social media. Unless information is coming from a credible news outlet, it is vital to do research before being swayed by a headline. Brainwashing prevention must occur internally as well. The brain is the most important organ in the human body. Prefrontal cortex function is a critical defense mechanism against brainwashing. Factors like stress, low educational achievement, and

REFERENCES

MEMORY AND ITS N

The Neurobiological Look on a Psy “Memory is the diary we all carry about with us.” Written by Oscar Wilde, this nineteenth century quote still rings true today. A life without memory, without things to recall, without mental time travel, would be bleak indeed; it would be without ideas, without knowledge, without reminiscing [1]. Accordingly, memory-related research is a popular area of interest within the field of neuropsychology, with increasing literature published within the last few decades. One category of memory that has recently drawn a lot of attention is episodic memory, a specific type of memory involving contextual and emotional information based around personal experiences.

These memories can range from anything like the memory of learning how to tie your shoelaces to the memory of failing a school exam. Episodic memory is especially influenced by stress, something that is ever-present in people’s lives in contemporary society [2]. There are two main types of stress - acute and chronic. Acute stress usually involves a short-term event, such as moving to a different city [2]. On the other hand, chronic stress is more common in daily life and more long-lasting - for example, financial hardship [2]. Considering the universality of stress, researchers are intrigued by the question about how something so common - stress - can affect something so fundamental to human life - episodic memory - in so many different ways. Matthew Sabia and Almut Hupbach, researchers from Lehigh University, conducted an experiment in 2020 to test the hypothesis that stress leads to the deterioration of episodic memory. This testing was based on the success or failure of one’s “scene memory.” Scene memory, which is indicated by the correct remembering of a scene, is used as a measure of episodic memory because of its contextual and experiential overlaps [3]. In this experiment, the scenes were of fifty objects superimposed onto three landscapes each for a total of 150 images. Methodology wise, the researchers divided their participant pool of 56 undergraduate students into two groups: one in which participants submerged their arm into a bucket of cold water intended to serve as a cold-pressure stressor (CPS), and another in which participants submerged their arm into warm water as a control. First, all participants were presented with one of the 150 scenes. Then, they were subjected to their treatment condition of either cold or warm water, and 48 hours later they were asked to recall the scene they saw. [3]. To judge participant stress levels, cortisol, a bodily hormone released during stress and arousal, was measured twice over the course of the experiment - once immediately after the treatment condition was administered, and once at the time of recall. Salivary tests showed a significant increase in cortisol in the CPS group relative to the control group immediately after CPS was applied, and a return to baseline levels just before the recall test [3]. Within the CPS group itself, some individ-

NUANCES:

ychological Problem uals experienced higher elevations of cortisol than others, effectively dividing the experimental group (those who received CPS) into two partitions. Those in the CPS group who did experience a high cortisol level performed worse on subsequent memory tests than those who did not. Therefore, it seems that one’s experience of stress is very important during memory consolidation - specifically, as cortisol levels increase, performance on memory tasks decreases [3]. Besides studying the effects of stress on episodic memory, it is important to understand the underlying mechanisms of how these memories are formed. Two systems exist for the processing of episodic memory in the human brain: the hippocampal system for cognitive and contextual memories like playing on a park swing during one’s childhood, and the striatal system for habitual and learning memories, like children learning they can attain a desired effect by throwing a tantrum [4]. In a 2016 paper, Stephanie Gagnon and Anthony Wagner contested that these memory systems are related, yet distinct because of their different functions. While the hippocampal system primarily focuses on contextual and recollective memories, the striatal system focuses more on stimulus-response associative memories [4]. It is important to note that both hippocampal and striatal systems are employed in typical tasks of episodic memory; for example, a more detailed memory of visiting the park could include how you felt dizzy after swinging too many times, which led to an avoidance of this particular behavior. In this example, both the hippocampal and striatal systems were employed - the hippocampal system through remembering details such as the color of the grass or the number of trees, and the striatal system through remembering how swinging too many times induced nausea. While the memory of the green grass is a contextual memory, the memory of the nauseating feeling following excessive swinging is a stimulus-response associative memory.

Written by Ally Lin Illustrated by Lizka Vaintrob

elevated levels of cortisol negatively impacted hippocampal processing, which was then accompanied by increased retention of emotionally salient information. Information presented by Goldfarb and Phelps showed that stress often affects the stimulus-response memory of the striatal system, allowing it to override the hippocampal system to become the dominant memory system [5]. This higher retention only applies to emotional memory, which lacks the contextual element. Metabolically speaking, stress induces an increase in catecholamines, hormones that ultimately operate on two main pathways: stimulation of cortisol production, which limits the hippocampal system, and activation of the basolateral amygdala, which increases the processing of emotional memory and stimulus-response memory in the striatum [5]. In the episodic memory example of going to the park, the memory of

A review paper published by Elizabeth Goldfarb and Elizabeth Phelps in 2017 suggested that there is more interaction between the two memory systems than initially thought under certain conditions, such as circumstances that involve stressful experiences [5]. Importantly, cortisol increases associated with stress can cause dramatic changes in activity [5]. For example, researchers found that stress reduces the brain’s engagement with the hippocampal system in favor of the striatal system for tasks of memory where traditionally, both systems would have been involved. The stress-induced

the way the blades of grass were swaying in the wind is buffeted by the stronger memory of nausea caused by swinging excessively on the swingset. This example demonstrates how emotional memory overtakes contextual memory in times of stress. An increase in cortisol also leads to impaired cell function as well as cell death in the hippocampus, causing further deficits in hippocampal processing ability [5]. Additionally, higher amounts of cortisol can also compromise blood flow in memory regions, like the parahippocampal gyrus and hippocampus of the hippocampal system [4]. Less blood flow to certain areas means lower energy being provided to that area and therefore decreased function of the structures in question. Studies on stress-induced loss of episodic memory delineate between recognition and recollection, where recognition refers to simple familiarity and recollection refers to remembering the contextual elements of the entire memory. Although the contextual elements in memory derive from the hippocampus, familiarity-based recognition (i.e. not complex recollection) can be obtained through activation of the striatum. When the striatum is activated by stress, the contextual element of memory is thus removed [3] in favor of facilitating association [5,6]. The extant literature on this topic elucidates a notion that a stressor can not only tip the scales in favor of the striatal system for memory, but also contribute to the weakening of the hippocampal network and contextual memory. Ultimately, the findings surrounding the nuances between the hippocampal and striatal systems of memory have important implications beyond the laboratory and into the clinical setting as well. Gagnon and Wagner discuss a study where individuals suffering from chronic stress (e.g. patients with PTSD) show reduced hippocampal volume and an inability to perform tasks of memory that involve detailed, contextual information [4]. Treatments for PTSD patients now include cortisol therapy, which can block episodic memory in the retrieval of traumatic events, limiting the occurrence of nightmares [4]. Other opportunities for rehabilitation after hippocampal damage due to stress may rely upon a more thorough understanding of specific memory mechanisms. One example of a strategy is using neural exercises (such as recalling detailed memories or chronologically labeling one’s own experiences) to stimulate the hippocampal system, in an effort to induce neuroplasticity that would allow for the striatal system to compensate for deficiencies in the hippocampal system. Another option is the application of cognitive behavioral therapy in an attempt to mediate the interactions of negative thoughts and actions, as seen in certain treatment options for depression. In any case, it remains paramount for the neuropsychological and scientific community at large to keep the memory systems, with their nuanced interactions and distinctions, in mind as researchers move forward in conducting relevant studies.

REFERENCES [1] Kristian Cereno. (2018). The Importance of Memories. Available from: https://www.albertafilipinojournal. com/2018/05/15/the-importance-of-memories/#:~:text=Memories%20are%20very%20essential%20in,us%20 feel%20happy%20and%20entertained.&text=By%20having%20memories%2C%20we%20will,right%20and%20 what%20is%20wrong [Accessed: 8/4/2021]. [2] American Psychological Association. (2018). APA: 3 Types of Stress. Available from: https://crmhs.org/apa-3types-of-stress/ [Accessed: 8/4/2021]. [3] Sabia, M., & Hupbach, A. (2020). Stress-Induced Increase in Cortisol Negatively Affects the Consolidation of Contextual Elements of Episodic Memories. Brain Sciences, 10(6), 358. [4] Gagnon, S. A., & Wagner, A. D. (2016). Acute stress and episodic memory retrieval:neurobiological mechanisms and behavioral consequences. Annals of the New York Academy of Sciences, 1369(1), 55-75. [5] Goldfarb, E. V., & Phelps, E. A. (2017). Stress and the trade-off between hippocampal and striatal memory. Current Opinion in Behavioral Sciences, 14, 47-53.

the

m i s e t r h y C

written by

of a

Clare Nimura

Chocolate CHIP COOKIE

Over time, humans have found many ways to transform raw foods to make them more appetizing and nutritious. Cooking raw eggs and meat breaks down proteins and makes them easier to digest. Cooking vegetables breaks down the cell walls of the plants, releasing more nutrients and minerals for our bodies to absorb and use. But our diets consist of more than just meat and veggies. Many foods, such as

butter (1.25 sticks) Butter is the preferred type of fat over margarine or shortening. Not only is it essential for flavor, adding nutty butterscotch notes, it also has a lower melting point than other solid cooking fats, which causes the dough to spread more during baking and makes for a thinner, crispier cookie. Butter is also a source of water in the dough, which is important for dissolving the hydrophilic sugar molecules [1]. In addition, creaming the butter and sugar together at the beginning of the process adds air to the mixture, which helps the cookies to rise as the air heats and expands in the oven. The process of introducing air into the internal structure of baked goods is called leavening, and is usually done with water vapor or carbon dioxide gas. Later on, when flour is added to the mixture, fat from the butter coats some of the flour and prevents it from interacting with water to develop gluten, thus making sure the final cookie is tender and crumbly rather than chewy and bread-like [2].

illustrations by

Aeja rosette

pasta and cheese, require more complex processes to prepare, and baking is one of the most complicated examples: it requires precise measurements, temperatures, and many types of ingredients. Here, we will take a deeper look into the science behind making the perfect chocolate chip cookie—crispy on the outside, chewy on the inside. First, the ingredients:

baking powder Baking SOda (1 teaspoon of power and 3/4 teaspoon of soda) Baking powder and baking soda are leaveners, which help the cookie rise by adding air to the internal structure. The egg proteins that capture water vapor and air provide some leavening effect, but these chemical leavening agents do most of the work. Baking soda, or sodium bicarbonate, is a basic powder. When it reacts with an acid, it rapidly breaks down into water, sodium, and carbon dioxide gas, which causes the cookie to rise as it is formed [1]. The acid comes from brown sugar, which is slightly acidic due to its molasses content. For this reason, cookies made with lots of brown sugar tend to rise more and be chewier, whereas cookies made with only white sugar are thinner and crispier. Baking powder, on the other hand, is a combination of both baking soda and an acidic component. In its powder form, baking powder is inert, but with the addition of water, the acidic and basic components react to produce bubbles of carbon dioxide, aerating the dough [2]. As in this recipe, a mixture of brown and white sugars is ideal because the acidic brown sugar will react with the basic baking soda to make the cookie rise, and the white sugar will make the cookie spread out so it does not get too cakey.

EGG

flour

(1 large)

(1.75 Cups of all-purpose flour)

Eggs are the main source of water in the recipe. The water interacts with proteins in flour, namely glutenin and gliadin, to form gluten, which helps give the cookie structure and allow it to rise taller [6]. Gluten is a stretchy, tough network of interconnected proteins that become more set and rigid with baking. Fats like butter inhibit the formation of gluten, ensuring that the final cookie is still tender and not tough. The more butter there is in a recipe, the less gluten will form, and the more the cookie will spread out rather than rise. The proteins in egg whites are also particularly good at trapping water vapor and air, keeping the cookies light, while the emulsified fat in egg yolks keeps the cookies tender [1].

The greater the proportion of flour relative to the wet ingredients, the crispier and crumblier the cookie will be. A shaped, brittle cookie like gingerbread has a high proportion of flour, while blondies have a lower proportion of flour, making them cakier in texture. Drop cookies like chocolate chip cookies fall somewhere in between: more flour will make a soft, thick, chewy cookie, and less flour will make a crumbly, thin, crisp cookie [2]. The proteins in flour help form the gluten network that gives the cookie structure and chewiness.

SUGAR (3/4 Cups & 2/3 cups of white sugar) Some recipes call for brown sugar, some for white sugar, and some use both, but what’s the difference? Typical white or granulated sugar is a crystallized version of the disaccharide sucrose, which consists of a glucose molecule and a fructose molecule linked together. Sucrose is slightly hygroscopic, meaning that it tends to retain some moisture [1]. Brown sugar is made of less refined crystals: it still contains appreciable amounts of glucose and fructose that have not crystallized into sucrose. Glucose and fructose are significantly more hygroscopic than sucrose, making brown sugar more moist and soft than white sugar. The brown color and distinct

taste come from molasses, a product of the sugar refining process; light brown sugar contains about 3.5 percent molasses and dark brown sugar contains about 6.5 percent molasses [34]. As the sugar melts at higher temperatures, it encourages the cookies to spread. Any sugar that was dissolved by water in the dough will caramelize when heated to give the cookies their golden brown color. Caramelization is the oxidation of sugar, a reaction which releases water as steam and produces a brown color [5]. Brown sugar undergoes the same processes as white sugar, but results in chewier, moister cookies because of its molasses content and hygroscopic qualities.

salt

chocolate

(3/4 teaspoon)

(6 OZ Dark chocolate, chopped)

Salt is a flavor-enhancer. It decreases water activity by binding to water molecules, concentrating the flavors and making aromatic molecules more volatile so the smell of freshly-baked cookies wafts out of the oven. Salt also suppresses bitterness and brings out sweet flavors [7].

True cookie connoisseurs will note that chocolate chips give the most even distribution of small pockets of chocolate throughout the cookie, while chopped chocolate or chocolate chunks lead to more chocolatey flavor throughout the cookie and more variation in texture [1]. The particular type of chocolate has minimal effect on the reactions happening in the rest of the cookie, so this final step is mostly baker’s choice.

IN THE OVEN Some people would be more than happy to eat the cookie dough itself, but an important series of chemical reactions happens when the dough is finally put in the oven to bake. The butter melts, causing the dough to spread out and release water, which turns to steam and forces the dough to rise. The proteins from the egg denature and give structure to the squishy dough. As water from the butter and egg evaporates,

the cookie dries out and cracks start to form on the surface. One of the last reactions that occurs before you take the cookies out of the oven is the Maillard reaction: proteins and sugars react to form molecules containing aromatic rings that give the cookies their golden brown color and aroma. Finally, the sugar caramelizes and the nutty, toasty notes of the cookie drift through the kitchen [8].

RECIPE Cream together the butter and sugar in a large bowl for 1-2 minutes until the mixture becomes pale, but not fluffy. Add the egg and mix until combined. In a medium bowl, mix together the dry ingredients, then fold the mixture into the wet ingredients using a rubber spatula until combined. Fold in the chocolate. Roll the dough into roughly 1¼ inch balls and refrigerate for at

least 12 hours. Place dough balls on baking sheets lined with parchment paper and bake at 350˚F for 13 minutes or until the cookies are puffed and golden. Take them out of the oven before the middle is completely set; they will continue to firm up as they cool [9].

references [1] López-Alt, J. K. (2020, August 25). The Food Lab: The Science of the Best Chocolate Chip Cookies. Retrieved March 30, 2021, from https://sweets. seriouseats.com/2013/12/the-food-lab-the-best-chocolate-chip-cookies.html [2] Joachim, D., & Schloss, A. (2018, July 19). The Science of Baking Cookies. Fine Cooking, (126). Retrieved March 30, 2021, from https://www.finecooking.com/article/thescience-of-baking-cookies-2 [3] Jampel, S. (2020, May 27). Light Versus Dark Brown Sugar: What’s the deal? Retrieved March 30, 2021, from https://www.bonappetit.com/story/lightversus-dark-brown-sugar [4] Gallary, C. (2019, May 02). Where Does the Brown in Brown Sugar Come From? Retrieved March 30, 2021, from https://www.thekitchn.com/where-doesthe-brown-in-brown-sugar-come-from-ingredient-intelligence-215952 [5] What is the caramelization? (n.d.). Retrieved March 30, 2021, from https:// www.scienceofcooking.com/caramelization.htm [6] Gluten: How Does it work? (2020, September 21). Retrieved March 30, 2021, from https://modernistcuisine.com/mc/gluten-how-does-itwork/#:~:text=Gluten%20is%20a%20protein%20found%20in%20wheat%20 products.&text=Gluten%20makes%20bread%20airy%20and,come%20into%20contact%20with%20water [7] Institute of Medicine (US) Committee on Strategies to Reduce Sodium Intake; Henney JE, Taylor CL, Boon CS, editors. Strategies to Reduce Sodium Intake in the United States. Washington (DC): National Academies Press (US); 2010. 3, Taste and Flavor Roles of Sodium in Foods: A Unique Challenge to Reducing Sodium Intake. Available from: https://www.ncbi.nlm.nih.gov/books/NBK50958/ [8] Warren, S. (Director). (2013, November). Transcript of “The Chemistry of Cookies” [Video file]. Retrieved March 30, 2021, from https:// www.ted.com/talks/stephanie_warren_the_chemistr y_of_cookies/ transcript?language=en#t-194750 [9] Druckman, C. (2020, October 21). Perfect Chocolate Chip Cookies. Retrieved March 30, 2021, from https://cooking.nytimes.com/ recipes/1021435-perfect-chocolate-chip-cookies?campaign_id=58&em_ pos=medium&emc=edit_ck_20201212&instance_id=24955&nl=cooking&nl_ art=2&ref=headline®i_id=81690778&segment_id=46761&te=1&user_ 31

The Protein Folding Q Written by Anuva Banwasi Illustrations by Kate Steiner

Proteins play key roles in our bodies, as antibodies binding to foreign invaders like bacteria or as enzymes catalyzing metabolic reactions. They are also a key component to a question in the field of biochemistry that has plagued scientists for over half a century on the exact folding mechanisms of proteins. While all proteins start out as a long chain of amino acids, each one has a distinct function that is governed by its three-dimensional structure. For example, the hemoglobin protein contains four amino acid chains, each of which has a heme group that carries iron to transport oxygen throughout the body [1]. Many other enzymes have specifically shaped active sites as well, where particular substrates bind and undergo reactions. The question at hand, commonly known as “the protein-folding problem,” is to predict a protein’s three-dimensinoal structure from just its amino acid sequence. In 1972, Christian Anfinsen found that “a completely unfolded protein could fold spontaneously to its biologically active state,” demonstrating the primary amino acid sequence completely defines protein structure [2]. However, predicting three-dimensional protein structures is challenging because amino acids can potentially combine into trillions of possible different shapes. In the past, scientists have applied several experimental techniques such as X-ray crystallography and cryo-electron microscopy to study protein structure. However, these techniques can be very expensive and time-consuming, taking anywhere from months to years to image and determine the structure of a single protein [2]. Cracking the protein-folding problem could revolutionize scientific research as well as clinical treatments. Protein misfolding is thought to be the cause of several diseases, including Alzheimer’s and Huntington’s disease. For instance, in Alzheimer’s disease, incorrectly folded proteins clump together in the brain and ultimately contribute to brain 32

atrophy[3]. With more advanced computational techniques with which to analyze protein structure, researchers could identify the specific amino acids responsible for the protein misfolding. This information could then be used to engineer treatments such as “pharmacoperones,” small hydrophobic molecules that bind to and fix misfolded proteins [4]. In addition to targeted drug delivery, having tools to study and predict protein structure could aid in the development of novel biomaterials, prosthetics, and more.

An Overview of Protein Folding At their core, proteins consist of a chain of amino acids that make up their primary structure. From here, the chains arrange themselves into secondary structures known as alpha helices and beta pleated sheets [5]. Alpha helices and beta sheets often have different sections that are hydrophobic or hydrophilic, leading to particular intermolecular attractive and repulsive forces that create each protein’s unique tertiary structure. In addition to hydrogen bonds and intermolecular forces, covalent bonds such as disulfide bridges that form between thiol groups also stabilize the protein [5]. A key point to solving the protein folding question is to view it as an energy problem [6]. Every possible three-dimensional structure of a protein has a different energy, and the goal is to select the most stable form, which often corresponds to the form that has the lowest amount of energy. From this perspective, the protein folding problem becomes simply an optimization or minimization problem. So why can’t we just try simulating all possible protein structures and find the lowest energy form? As mentioned above, proteins often consist of thousands of different amino acids that can combine in many different possible conformations [6]. Furthermore, with added variables of intermolecular interactions and angles between amino acids, there are just too many conformations for the computer to test.

Question The Rise of Machine Learning Recently, there have been significant advances in predicting protein structure using deep learning and artificial intelligence. Every two years since 1994, the National Institutes of Health has hosted the Critical Assessment of Techniques for Protein Structure Prediction (CASP), a biennial experiment in which researchers across academic and industry groups apply their structure prediction methods to investigate unknown protein structures. In 2018, Google’s AI unit DeepMind presented AlphaFold, an algorithm that applies neural networks to protein-structure prediction [7]. Recently in the November 2020 CASP conference, DeepMind announced AlphaFold2, a revision on its previous algorithm, that placed first in the competition [7].A protein can be thought of as a graph in space where the amino acids, also known as residues, are represented by nodes and the distances between the amino acids are represented as edges [7]. In addition to distance, another relevant piece of information to consider is the backbone torsional angles between amino acid chains. The goal of a deep learning algorithm like AlphaFold2 is to iteratively learn the pairwise distances and backbone torsional angles in a protein. These pairwise distances and torsional angles can then be used to construct the three-dimensional structure of the protein to an incredibly accurate degree [7]. One concept that is especially important to novel deep learning models like AlphaFold2 is a multiple sequence alignment (MSA). An MSA is an alignment of homologous protein sequences amongst different species [8]. Researchers have found that changes in a protein sequence are often linked. In other words, a change in one amino acid may often be associated with a change in another amino acid, producing certain combinations and patterns [8]. Thus, an MSA can be used to identify amino acids that are closely related or dependent on each other. Algorithms such as AlphaFold2 take advantage of these relationships, using the MSA as input to predict the pairwise distances between amino acids in a protein [9].

acids. This is where the application of machine learning is especially useful. In any machine learning model, we start by making a prediction and then refine the model’s parameters until the error between the prediction and actual or “ground truth” value is minimized [9]. In our particular problem, we have a set of training data where the pairwise distances between the amino acids are known. Thus, the model needs to refine itself until its predicted pairwise distances are as close as possible to the actual distances [9]. In order to perform this iterative refinement and predict pairwise distances between amino acids, scientists are applying a novel deep learning architecture known as transformers. Transformers have previously been used in natural language processing, translating a sequence of elements in one language to another language [10]. The architecture encodes the sequence in one language into its own internal representation, which is then decoded into the other language [10]. A key aspect of transformers is that they use self-attention. As a human reads a sentence, they keep track not only of the current word but also previous words in the sentence that aid in overall understanding. The attention mechanism is similar to this, taking into account the relevance of other elements in the input sequence during the encoding process [10]. With protein structure prediction, the MSA can tell us which amino acids depend on each other, similar to how words in a sentence relate to each other. This information can be used hand in hand with the attention-based transformer architecture to predict pairwise distances [9].

The truly interesting question is how the model uses these MSA sequences to predict the pairwise distances between amino 33

Looking Forward Deep learning models such as AlphaFold2 can now predict the pairwise distances and torsional angles between amino acids to reconstruct three-dimensional protein structure. However, there are still many interesting questions to further explore in the realm of protein structure prediction and machine learning. Specifically, one of the key challenges is optimizing algorithms to perform efficiently [11]. With transformers and self-attention, the problem can often scale-up to quadratic time complexity; in other words, the performance is proportional to the square of the input size. Therefore, many researchers are working on novel transformer architectures that can reduce the time complexity and improve efficiency [11]. The development of deep learning algorithms for protein structure prediction is clear evidence of the importance of technology in modern day medicine. With such tools, scientists and doctors can make new strides in understanding the protein folding mechanism and designing novel therapies for protein misfolding diseases such as Alzheimer’s disease.

References [1] Marengo-Rowe A. J. (2006). Structure-function relations of human hemoglobins. Proceedings (Baylor University. Medical Center), 19(3), 239–245. https://doi.org/10.1080/0899828 0.2006.11928171. [2] Rennie, G. Lawrence Livermore National Laboratory (2004, December 20). The Art of protein structure prediction. Retrieved from https://www.eurekalert.org/features/doe/2004-12/ ddoe-tao122204.php. [3] Ashraf, G. M., Greig, N., et al. (2014). Protein misfolding and aggregation in Alzheimer’s disease and type 2 diabetes mellitus. CNS & neurological disorders drug targets. https:// doi.org/10.2174/1871527313666140917095514. [4] Ulloa-Aguirre, A., & Michael Conn, P. (2011). Pharmacoperones: a new therapeutic approach for diseases caused by misfolded G protein-coupled receptors. Recent patents on endocrine, metabolic & immune drug discovery, 5(1), 13–24. https://doi.org/10.2174/187221411794351851. [5] Protein Folding. (2020, August 10). Retrieved March 29, 2021, from https://chem.libretexts.org/@go/page/496. [6] Norn, C., Wicky, B., et al. (2021, March 16). Protein sequence design by conformational landscape optimization. Proceedings of the National Academy of Sciences. https://doi. org/10.1073/pnas.2017228118. [7] Jumper, J., Evans, R., et al. (2020, December). High Accuracy Protein Structure Prediction Using Deep Learning. Retrieved from https://deepmind.com/blog/article/alphafold-a-solution-to-a-50-year-old-grand-challenge-in-biology. [8] Chatzou, M., Magis, C., et al. (2016, November). Multiple sequence alignment modeling: methods and applications, Briefings in Bioinformatics, Volume 17, Issue 6.. https://doi. org/10.1093/bib/bbv099 [9] Senior, A.W., Evans, R., Jumper, J. et al. (2020). Improved protein structure prediction using potentials from deep learning. Nature 577, 706–710. https://doi.org/10.1038/s41586-0191923-7. [10] Giacaglia, G. How Transformers Work. The Neural Network used by OpenAI and DeepMind. (2019, March) Retrieved from https://towardsdatascience.com/transformers-141e32e69591. [11] Ho, J., Kalchbrenner, N., Weissenborn, D., Salimans, T. (2019, December) Axial Attention in Multidimensional Transformers. arXiv:1912.12180.

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